Jun and Fos heterodimerize with ATFa, a member of the ATF/CREB family and modulate its transcriptional activity
| Autor: | B, Chatton, J L, Bocco, J, Goetz, M, Gaire, Y, Lutz, C, Kedinger |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Leucine Zippers
Base Sequence Transcription Genetic Proto-Oncogene Proteins c-jun Genetic Vectors Molecular Sequence Data Genes fos Blood Proteins DNA Transfection Activating Transcription Factors Cell Line Genes jun Isomerism Genes Reporter Animals Humans Amino Acid Sequence Cyclic AMP Response Element-Binding Protein Proto-Oncogene Proteins c-fos HeLa Cells Transcription Factors |
| Zdroj: | Oncogene. 9(2) |
| ISSN: | 0950-9232 |
| Popis: | Three related clones encoding proteins (ATFa1, 2 and 3) with specific ATF/CRE DNA-binding activities have been isolated from HeLa cell cDNA libraries. All three isoforms have weak effects on the basal activity of the adenovirus E2a promoter. We present evidence suggesting that a C-terminal element of the ATFa molecules negatively interferes with the intrinsic activation function of these proteins. We also show that coexpression of ATFa with c-Jun, Jun-B or Jun-D stimulates ATFa-dependent reporter activity, while coexpression of c-Fos has no effect. Deletion analyses indicate that the metal-binding region of ATFa is dispensible for this effect, but that the domain comprising the leucine-zipper region of ATFa is required. Reciprocal co-immunoprecipitation experiments and electrophoretic band-shift assays with in vitro synthesized proteins reveal direct interactions between ATFa and Jun or Fos. The ATFa/c-Jun heterodimers, but not the ATFa/c-Fos complexes, bind efficiently to ATF, CRE or AP1 sites. The detection of ATFa-Jun complexes in crude extracts from HeLa cells transfected with ATFa and c-Jun expression vectors suggests that such ATFa/c-Jun heterodimers also form in vivo. Altogether these results indicate that the ATFa proteins may contribute to the modulation of the activity of the Jun/Fos complexes by altering their DNA-binding and transcriptional properties. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|